The program project " Genital Tract in HIV pathogenesis" will investigate immunologic, and host factors in the female genital microenvironment that influence HIV infectivity and susceptibility. This program project integrates three research projects and three Core facilities. Subproject 0001, "Bacterial Vaginosis ( BV) and HIV in the Female Genital Tract" proposes that BV in the genital tract increases HIV susceptibility and will assess the effects or organisms associated with BV on HIV expression. Subproject 0002, "Female Genital Tract Immunity and HIV vaccine responses" focuses on HIV specific vaccination, and the role of pre-existing genital tract HIV immunity in the response to immunization. Subproject 0002, "HIV-1 Susceptibility Factors in Cervical Secretions" will focus on the microbiology/immunology of the cervical microenvironment and how secreted and microbial factors inhibit or enhance susceptibility to HIV infection in the female genital tract. The projects will utilize the well established HIV cohorts (REACH, WIHS, WITS) spanning ages from adolescence to adulthood and the spectrum of HIV infection from asymptomatic to AIDS as well as two nigh risk seronegative cohorts. The research projects are supported by three Cores: Statistics and Data Management Core coordinating research, scientific meetings and data management support; the Clinical Core managing subject recruitment, existing cohort utilization and clinical data collection; and the Laboratory Core establishing a specimen repository and providing virologic and immunologic assays. By characterizing factors affecting HIV infectivity and susceptibility to infection, the studies will increase our understanding of sexual and perinatal HIV transmission and contribute to future therapy and vaccine strategies.